Discovery of Pyrazole-5-yl-amide Derivatives Containing Cinnamamide Structural Fragments as Potential Succinate Dehydrogenase Inhibitors

• DOI: 10.1021/acs.jafc.3c04355
• Publication Date: 2023-11-03T16:17:21Z
• Authors: Xiang Cheng; Zonghan Xu; Hongyun Cui; Zhen Zhang; Wei Chen; Fanglei Wang; Shanlu Li; Qixuan Liu; Dandan Wang; Xianhai Lv; Xihao Chang
• Keywords: EC50; Amide; Lead compound

To promote the development of novel agricultural succinate dehydrogenase inhibitor (SDHI) fungicides, we introduced cinnamamide and nicotinamide structural fragments into structure pyrazol-5-yl-amide by carbon chain extension scaffold hopping, respectively, synthesized a series derivatives. The results biological activity assays indicated that most target compounds exhibited varying degrees inhibitory against tested fungi. Notably, G22, G28, G34, G38, G39 excellent in vitro antifungal activities Valsa mali with EC50 values 0.48, 0.86, 0.57, 0.73, 0.87 mg/L, this result was significantly more potent than boscalid (EC50 = 2.80 mg/L) closer to specialty control drug tebuconazole 0.30 mg/L). Compounds G22 G34 also vivo protective curative effects V. at 40 mg/L. SEM TEM observations may affect normal mycelial morphology as well cellular ultrastructure. Molecular docking analysis possessed similar binding mode SDH, detailed SDH inhibition validated feasibility designed potential inhibitors. G3 were selected for theoretical calculations, terminal carboxylic acid group be key region influencing activity. Furthermore, toxicity tests on Apis mellifera l. revealed low A. populations. above demonstrated these pyrazole-5-yl-amide derivatives are promising low-risk drug-resistance SDHI fungicides.